Studies are proposed to define the molecular and functional interactions of the factor VIII molecular complex in normal hemostasis. The specific aims of these investigations are: 1) to characterize the interaction of plasma factor VIII and its putative platelet membrane receptor, glycoprotein Ib, 2) to characterize the structural and biochemical interactions of platelet factor VIII, and 3) to define the role of factor VIII-related antigen as a functional and regulatory protein for VIII C and the significance of this interaction to normal hemostasis. Monoclonal antibodies to GPIb, GPIIb/IIIa, VIIIR:Ag, and VIII C -- currently available in the investigators' laboratory-- will be used to study the molecular interactions between factor VIII and platelets under physiologic conditions. New techniques have been developed to screen hybridoma culture fluids using whole plasma and a second heterologous antibody, thus obviating the need for pure antigen. The proposed studies will enable more knowledge to be gained concerning the interaction of these two proteins in normal hemostasis and in hemophilia and von Willebrand's disease. A long-term goal is the development of improved therapeutic products for patients with these common coagulation disorders.